TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5095	15508;15509;15510	chr2:178734541;178734540;178734539	chr2:179599268;179599267;179599266
N2AB	4778	14557;14558;14559	chr2:178734541;178734540;178734539	chr2:179599268;179599267;179599266
N2A	3851	11776;11777;11778	chr2:178734541;178734540;178734539	chr2:179599268;179599267;179599266
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-34
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.3749
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Q/K	None	None	0.165	N	0.524	0.226	0.212008924253	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
Q/R	rs2081098001	None	0.324	N	0.489	0.314	0.223847106136	gnomAD-4.0.0	1.50954E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.98325E-05	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Q/A	0.2876	likely_benign	0.2249	benign	-0.673	Destabilizing	0.207	N	0.467	neutral	None	None	None	None	N
Q/C	0.5468	ambiguous	0.446	ambiguous	-0.055	Destabilizing	0.981	D	0.612	neutral	None	None	None	None	N
Q/D	0.4908	ambiguous	0.3689	ambiguous	-0.699	Destabilizing	0.116	N	0.479	neutral	None	None	None	None	N
Q/E	0.0862	likely_benign	0.0833	benign	-0.565	Destabilizing	0.001	N	0.268	neutral	N	0.404789091	None	None	N
Q/F	0.6266	likely_pathogenic	0.5539	ambiguous	-0.139	Destabilizing	0.69	D	0.603	neutral	None	None	None	None	N
Q/G	0.3652	ambiguous	0.2807	benign	-1.071	Destabilizing	0.388	N	0.539	neutral	None	None	None	None	N
Q/H	0.172	likely_benign	0.1442	benign	-0.847	Destabilizing	0.001	N	0.373	neutral	N	0.496167006	None	None	N
Q/I	0.4006	ambiguous	0.3429	ambiguous	0.366	Stabilizing	0.818	D	0.609	neutral	None	None	None	None	N
Q/K	0.1129	likely_benign	0.102	benign	-0.6	Destabilizing	0.165	N	0.524	neutral	N	0.500179425	None	None	N
Q/L	0.1539	likely_benign	0.124	benign	0.366	Stabilizing	0.324	N	0.539	neutral	N	0.502026202	None	None	N
Q/M	0.398	ambiguous	0.3513	ambiguous	0.699	Stabilizing	0.932	D	0.545	neutral	None	None	None	None	N
Q/N	0.3311	likely_benign	0.2602	benign	-1.116	Destabilizing	0.241	N	0.463	neutral	None	None	None	None	N
Q/P	0.5282	ambiguous	0.3006	benign	0.051	Stabilizing	0.492	N	0.563	neutral	N	0.508801056	None	None	N
Q/R	0.1049	likely_benign	0.0916	benign	-0.593	Destabilizing	0.324	N	0.489	neutral	N	0.491038541	None	None	N
Q/S	0.271	likely_benign	0.2097	benign	-1.221	Destabilizing	0.207	N	0.481	neutral	None	None	None	None	N
Q/T	0.2196	likely_benign	0.1756	benign	-0.894	Destabilizing	0.563	D	0.486	neutral	None	None	None	None	N
Q/V	0.2715	likely_benign	0.2213	benign	0.051	Stabilizing	0.563	D	0.565	neutral	None	None	None	None	N
Q/W	0.4532	ambiguous	0.3939	ambiguous	-0.066	Destabilizing	0.981	D	0.623	neutral	None	None	None	None	N
Q/Y	0.3687	ambiguous	0.3236	benign	0.142	Stabilizing	0.527	D	0.593	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.